Spectroscopic unwanted signal filters for discrimination of vulnerable plaque and method therefor

Abstract

Spectral variation contributed from the absorbance of unwanted correlated signals, such as blood at variable pathlengths between an in vivo catheter optic probe and a coronary vessel wall is an obstacle in the detection of vulnerable plaque. Preprocessing methods are described to reduce the impact of blood upon the spectral signal, based on the principles of Orthogonal Subspace Projection (OSP) and Generalized Least Square (GLS). The multivariate discrimination models used on the processed spectral information reduce the number of independent factors that include contributions from blood. The disclosed chemometric processing including preprocessing methods provide for in vivo spectral detection of medical analytes within the human body and in particular within the coronary vessel wall. A demonstration of how the preprocessing methods impact a discrimination modeling technique is provided, how the blood filters were developed and optimized, and finally how the OSP and GLS blood filters correct the spectral signal and improve the discrimination results of the models.

1. A method for analyzing blood vessels in the presence of intervening unwanted spectral signal, the method comprising:
 irradiating blood vessel walls through intervening fluid; 
 collecting spectral responses; 
 determining spectral responses of the blood vessel walls from the collected spectral responses by applying a filter generated using a spectral response of the intervening fluid to remove or deemphasize a contribution of the intervening fluid relative to a signal from the blood vessel walls; and 
 assessing states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls. 
 
     
     
       2. A method as claimed in  claim 1 , wherein the step of irradiating comprises illuminating the blood vessel walls with an optical source. 
     
     
       3. A method as claimed in  claim 2 , wherein the optical source generates near infrared light. 
     
     
       4. A method as claimed in  claim 1 , wherein the step of collecting the spectral responses comprises detecting returning radiation to a catheter head. 
     
     
       5. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is collected at a relatively large distance from the blood vessel walls. 
     
     
       6. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is collected in a reference well, ex vivo. 
     
     
       7. A method as claimed in  claim 1 , wherein the filter is based on a generalized least squares analysis. 
     
     
       8. A method as claimed in  claim 7 , wherein parameters of the generalized least squares filter are optimized by analyzing a performance of the filter in improving an accuracy of a qualification analysis, such as a discrimination or classification, or a quantitative analysis. 
     
     
       9. A method as claimed in  claim 1 , wherein the filter is based on an orthogonal subspace projection analysis. 
     
     
       10. A method as claimed in  claim 9 , wherein a subspace projection dimension of the filter is optimized by analyzing a performance of the filter in improving an accuracy of a qualification analysis, such as a discrimination or classification process, or a quantitative analysis. 
     
     
       11. A method as claimed in  claim 1 , wherein the intervening fluid is blood. 
     
     
       12. A method as claimed in  claim 1 , wherein the intervening fluid is a fluid used to flush blood along a path to the blood vessel walls. 
     
     
       13. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is determined from blood samples of multiple individuals. 
     
     
       14. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is determined from blood samples of the current patient. 
     
     
       15. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is determined from blood samples of the current patient and other individuals. 
     
     
       16. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is determined by gathering a spectral response of a contrast agent. 
     
     
       17. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is determined by gathering a spectral response of an artificial blood. 
     
     
       18. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is determined by gathering a spectral response of a flushing agent such as saline solution. 
     
     
       19. A method as claimed in  claim 1 , wherein the spectral response of the intervening fluid is determined by gathering a spectral response of a fluid, such as a gas or liquid, that is used to expand a balloon catheter. 
     
     
       20. A method as claimed in  claim 1 , wherein the step of assessing states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls comprises determining whether the blood vessel walls are comprised of vulnerable or non-vulnerable plaques. 
     
     
       21. A method as claimed in  claim 1 , wherein the step of assessing states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls comprises determining whether the blood vessel walls are comprised of atheromas or normal tissue. 
     
     
       22. A method as claimed in  claim 1 , wherein the step of assessing states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls comprises applying multivariate regression techniques. 
     
     
       23. A method as claimed in  claim 1 , wherein the step of assessing states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls comprises classifying a state of the vessel walls. 
     
     
       24. A method as claimed in  claim 1 , wherein the step of assessing states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls comprises relating the determined spectral responses with spectral responses of vessel walls in a state of interest. 
     
     
       25. A method as claimed in  claim 1 , wherein the step of assessing states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls comprises classifying states of the vessel walls by relating the determined spectral responses with spectral responses of vessels walls in different states. 
     
     
       26. A method as claimed in  claim 1 , wherein the step of determining the spectral responses of the blood vessels walls comprises processing the collected spectra, being a composite of the intervening fluid and blood vessel walls, in an analyzer after detection of the collected spectral responses to remove or deemphasize the contribution of the intervening fluid. 
     
     
       27. A system for analyzing blood vessels in the presence of intervening fluid, the system comprising:
 a source of radiation; 
 a catheter for directing the radiation at blood vessel walls through intervening fluid and collecting radiation from the blood vessel walls; 
 a detector system of monitoring the collected radiation; 
 a controller for generating spectral responses from the collected radiation detected by the detector system; 
 an analyzer for determining spectral responses of the blood vessel walls from the collected spectral responses from the controller and generating information for assessment of the blood vessel walls in response to the determined spectral responses of the blood vessel walls, wherein the analyzer determines the spectral responses of the blood vessel walls by applying a filter generated in response to spectra of the fluid to remove a contribution of the fluid. 
 
     
     
       28. A system as claimed in  claim 27 , wherein the source comprises an optical source. 
     
     
       29. A system as claimed in  claim 27 , wherein the source comprises a near infrared source. 
     
     
       30. A system as claimed in  claim 27 , wherein the spectra of the fluid is collected when a head of the catheter is at a relatively large distance from the blood vessel walls. 
     
     
       31. A system as claimed in  claim 27 , wherein the spectra of the fluid is collected in a reference well, ex vivo. 
     
     
       32. A system as claimed in  claim 27 , wherein the filter is based on a generalized least squares analysis. 
     
     
       33. A system as claimed in  claim 32 , wherein parameters of the generalized least squares filter are optimized by analyzing a performance of the filter in improving the assessment of a state of the blood vessel walls by the analyzer. 
     
     
       34. A system as claimed in  claim 27 , wherein the filter is based on an orthogonal subspace projection analysis. 
     
     
       35. A system as claimed in  claim 34 , wherein a subspace projection dimension of the filter is optimized by analyzing a performance of the filter in improving an accuracy of a discrimination process. 
     
     
       36. A system as claimed in  claim 27 , wherein the analyzer assesses states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls by determining whether the blood vessel walls is comprised of vulnerable or non-vulnerable plaques. 
     
     
       37. A system as claimed in  claim 27 , wherein the analyzer assesses states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls by determining whether the blood vessel walls are comprised of atheromas or normal tissue. 
     
     
       38. A system as claimed in  claim 27 , wherein the analyzer assesses states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls by applying multivariate regression techniques. 
     
     
       39. A system as claimed in  claim 27 , wherein the analyzer provides a quantitative assessment of the blood vessel walls to an operator. 
     
     
       40. A system as claimed in  claim 27 , wherein the analyzer assesses states of the blood vessel walls in response to the determined spectral responses of the blood vessel walls by relating the determined spectral responses with spectral responses of vessels walls in different states. 
     
     
       41. A method for de-emphasizing a blood response in a spectral response of a structure of interest, the method comprising:
 generating a filter determined by spectra representing a response of the blood which is collected at a relatively large distance from the structure of interest through the blood; and 
 applying the filter to a collected spectral response including the blood response to generate the spectral response of the structure of interest. 
 
     
     
       42. A system for spectrally analyzing interior structures of animals in the presence of unwanted spectral signal sources, the system comprising:
 a source of radiation; 
 a catheter for directing the radiation at the interior structures through intervening medium and collecting radiation returning from the interior structures; 
 detector system of monitoring radiation from the interior structures; 
 a spectrometer controller for generating spectral responses from the monitored radiation detected by the detector system; 
 an analyzer for determining spectral responses of the interior structures from the generated spectral responses from the spectrometer controller by removing a contribution of the medium by applying a filter generated using a spectral response of the medium to remove or deemphasize a contribution of the medium relative to a signal from the interior structures and generating an assessment of a state of the internal structures in response to the determined spectral responses of the internal structures. 
 
     
     
       43. A blood vessel analysis method comprising:
 collecting spectral responses of the blood vessels, the spectral responses including unwanted spectral signals caused by irradiating the blood vessel through an intervening fluid; 
 processing the spectral responses by applying a filter generated from the unwanted spectral signals to reduce the unwanted spectral signals relative to the blood vessel responses to generate determined spectral responses of the blood vessels; and 
 using the determined spectral responses to analyze the blood vessels. 
 
     
     
       44. A method as claimed in  claim 43 , wherein the step of collecting comprises irradiating the blood vessels with optical radiation. 
     
     
       45. A method as claimed in  claim 43 , wherein the step of collecting comprises irradiating the blood vessels with near infrared radiation. 
     
     
       46. A method as claimed in  claim 43 , further comprising processing the spectral responses to remove offsets and/or slopes. 
     
     
       47. A method as claimed in  claim 43 , further comprising processing the spectral responses to eliminate sources of variation of the signal not related to signal of interest. 
     
     
       48. A method as claimed in  claim 43 , further comprising processing the spectral responses by normalizing and/or autoscaling. 
     
     
       49. A method as claimed in  claim 43 , further comprising processing the spectral responses to enhance the spectral signal. 
     
     
       50. A method as claimed in  claim 43 , further comprising processing the spectral responses by mean centering the responses. 
     
     
       51. A method as claimed in  claim 43 , further comprising processing the spectral responses by detrending the responses. 
     
     
       52. A method as claimed in  claim 43 , further comprising processing the spectral responses to reduce random noise or unwanted signal that may be caused by instrumental responses using smoothing techniques. 
     
     
       53. A method as claimed in  claim 43 , further comprising processing the spectral responses to reduce random noise or unwanted signal that may be caused by instrumental responses using Savitsky-Golay smoothing. 
     
     
       54. A method as claimed in  claim 43 , further comprising processing the spectral responses to remove multiplicative effects. 
     
     
       55. A method as claimed in  claim 43 , further comprising processing the spectral responses using standard normal variance (SNV) analysis. 
     
     
       56. A method as claimed in  claim 43 , further comprising processing the spectral responses using multiplicative signal or scatter correction (MSC) analysis. 
     
     
       57. A method as claimed in  claim 43 , wherein the step of using the determined spectral responses to analyze the blood vessels comprises applying multivariate analysis for a qualification analysis, such as discrimination and classification, of the blood vessels. 
     
     
       58. A method as claimed in  claim 57 , wherein the multivariate analysis includes Principal Component Analysis. 
     
     
       59. A method as claimed in  claim 57 , wherein the multivariate analysis includes Principal Component Analysis combined with a statistical boundary, such as Mahalanobis distance. 
     
     
       60. A method as claimed in  claim 57 , wherein the multivariate analysis includes Principal Component Analysis combined with a residual analysis and a statistical boundary, such as Mahalanobis distance. 
     
     
       61. A method as claimed in  claim 57 , wherein the multivariate analysis includes Partial Least Squares Discriminant Analysis. 
     
     
       62. A method as claimed in  claim 43 , wherein the step of using the determined spectral responses to analyze the blood vessels comprises applying multivariate analysis for quantification of a state of the blood vessels. 
     
     
       63. A method as claimed in  claim 62 , wherein the multivariate analysis includes using Partial Least Squares analysis. 
     
     
       64. A method as claimed in  claim 43 , wherein the step of using the determined spectral responses to analyze the blood vessels comprises applying machine language learning for discrimination or classification of a state of the blood vessels. 
     
     
       65. A method as claimed in  claim 64 , wherein the machine language analysis includes using support vector machine analysis. 
     
     
       66. A method as claimed in  claim 64 , wherein the machine language analysis includes using artificial neural networks analysis. 
     
     
       67. A method as claimed in  claim 43 , wherein the step of processing the spectral responses comprises up-weighting the blood vessel responses. 
     
     
       68. A method as claimed in  claim 43 , wherein the step of processing the spectral responses comprises down-weighting the unwanted spectral signal. 
     
     
       69. A method as claimed in  claim 43 , wherein the step of processing the spectral responses comprises up-weighting the blood vessel responses and comprises down-weighting the unwanted spectral signal, in either order. 
     
     
       70. A method as claimed in  claim 43 , wherein the step of collecting the spectral responses comprise irradiating the blood vessels using a catheter. 
     
     
       71. A method as claimed in  claim 43 , wherein the unwanted spectral signal is generated at least in part by temperature fluctuation, heart motion, and/or catheter motion. 
     
     
       72. A method as claimed in  claim 1 , wherein the step of processing the spectral responses comprises processing the collected spectral responses, being a composite of intervening fluid and blood vessel walls, in an analyzer after detection of the collected spectral responses to remove or deemphasize the unwanted spectral signals.